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Basic Characteristics of Mutations
|
|
Mutation Site
|
V22A |
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Mutation Site Sentence
|
However, of the three in which specific changes could be assigned to loss of function, these mapped to conserved residues in the first alpha helix of the Vpu cytoplasmic tail (n = 1) and transmembrane region (n = 2), specifically I17T, V22A and I39L. |
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Mutation Level
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Amino acid level |
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Mutation Type
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Nonsynonymous substitution |
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Gene/Protein/Region
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Vpu |
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Standardized Encoding Gene
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Vpu
|
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Genotype/Subtype
|
HIV-1 B |
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Viral Reference
|
NL4.3
|
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Functional Impact and Mechanisms
|
|
Disease
|
HIV Infections
|
|
Immune
|
Y |
|
Target Gene
|
CD8A
CD4
BST2
NFKB1
|
|
Clinical and Epidemiological Correlations
|
|
Clinical Information
|
Y |
|
Treatment
|
- |
|
Location
|
USA |
|
Literature Information
|
|
PMID
|
24465210
|
|
Title
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Preservation of tetherin and CD4 counter-activities in circulating Vpu alleles despite extensive sequence variation within HIV-1 infected individuals
|
|
Author
|
Pickering S,Hue S,Kim EY,Reddy S,Wolinsky SM,Neil SJ
|
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Journal
|
PLoS pathogens
|
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Journal Info
|
2014 Jan;10(1):e1003895
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Abstract
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The HIV-1 Vpu protein is expressed from a bi-cistronic message late in the viral life cycle. It functions during viral assembly to maximise infectious virus release by targeting CD4 for proteosomal degradation and counteracting the antiviral protein tetherin (BST2/CD317). Single genome analysis of vpu repertoires throughout infection in 14 individuals infected with HIV-1 clade B revealed extensive amino acid diversity of the Vpu protein. For the most part, this variation in Vpu increases over the course of infection and is associated with predicted epitopes of the individual's MHC class I haplotype, suggesting CD8+ T cell pressure is the major driver of Vpu sequence diversity within the host. Despite this variability, the Vpu functions of targeting CD4 and counteracting both physical virus restriction and NF-kappaB activation by tetherin are rigorously maintained throughout HIV-1 infection. Only a minority of circulating alleles bear lesions in either of these activities at any given time, suggesting functional Vpu mutants are heavily selected against even at later stages of infection. Comparison of Vpu proteins defective for one or several functions reveals novel determinants of CD4 downregulation, counteraction of tetherin restriction, and inhibition of NF-kappaB signalling. These data affirm the importance of Vpu functions for in vivo persistence of HIV-1 within infected individuals, not simply for transmission, and highlight its potential as a target for antiviral therapy.
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Sequence Data
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-
|